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The title compound, C14H13BrO3, is an inter­mediate in the preparation of naproxen, a non-steroidal anti-inflammatory drug (NSAID). Geometric parameters are in the usual ranges. Neglecting the H atoms, the mol­ecule comprises two planar halves, the bromo­naphthyl moiety (r.m.s. deviation = 0.010 Å) and the ethoxy­carbonyl­meth­oxy moiety (r.m.s. deviation = 0.018 Å). The dihedral angle between these is 79.23 (7)°. The crystal packing is stabilized by a weak C—H...O hydrogen bond.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807052300/at2442sup1.cif
Contains datablocks I, global

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S1600536807052300/at2442Isup2.hkl
Contains datablock I

CCDC reference: 667451

Key indicators

  • Single-crystal X-ray study
  • T = 173 K
  • Mean [sigma](Wave) = 0.000 Å
  • R factor = 0.040
  • wR factor = 0.103
  • Data-to-parameter ratio = 14.5

checkCIF/PLATON results

No syntax errors found



Alert level G ABSTM02_ALERT_3_G When printed, the submitted absorption T values will be replaced by the scaled T values. Since the ratio of scaled T's is identical to the ratio of reported T values, the scaling does not imply a change to the absorption corrections used in the study. Ratio of Tmax expected/reported 0.912 Tmax scaled 0.483 Tmin scaled 0.402
0 ALERT level A = In general: serious problem 0 ALERT level B = Potentially serious problem 0 ALERT level C = Check and explain 1 ALERT level G = General alerts; check 0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data 0 ALERT type 2 Indicator that the structure model may be wrong or deficient 1 ALERT type 3 Indicator that the structure quality may be low 0 ALERT type 4 Improvement, methodology, query or suggestion 0 ALERT type 5 Informative message, check

Comment top

The title compound is an intermediate in the preparation of naproxen, a non-steroidal anti-inflammatory drug (NSAID) commonly used for the reduction of high to extreme pain, fever, inflammation and stiffness caused by conditions such as osteoarthritis, rheumatoid arthritis, psoriatic arthritis, gout, ankylosing spondylitis, injury. Naproxen is a member of the 2-arylpropionic acid (profen) family of NSAIDs. The structures the related compounds viz., naproxen (Ravikumar et al., 1985), 6-methoxy-2-naphthyl acetic acid ester-glycolamide (Sharma et al., 2004), 1-(5-chloro-6-methoxynaphthalen-2-yl)propan-1-one (Ye et al., 2006), complex of a lisuride derivative and (S)-naproxen (Bachechi et al., 1997), absolute configuration of (R)-1-phenylethylammonium (S)-2-(6-methoxy-2-naphthyl)propionate (Dupont et al., 1996), N'-isopropylidene-6-methoxy-2-naphthohydrazide (Sarojini et al., 2007), ethyl 6-methoxy-2-naphthoate (Yathirajan et al., 2007) have been published. A new derivative was prepared and its crystal structure is reported.

Geometric parameters of the title compound are in the usual ranges. Neglecting the H atoms, the molecule comprises two planar halves, the bromonaphthyl moiety [r.m.s. deviation 0.010 Å] and the ethoxycarbonylmethoxy moiety [r.m.s. deviation 0.018 Å]. The dihedral angle between these moieties is 79.23 (7)°. The crystal packing is stabilized by a weak C—H···O hydrogen bond.

Related literature top

For related literature, see: Bachechi et al. (1997); Dupont et al. (1996); Ravikumar et al. (1985); Sarojini et al. (2007); Sharma et al. (2004); Yathirajan et al. (2007); Ye et al. (2006).

Experimental top

A mixture of 6-bromo-2-hydroxynaphthalein (2.23 g, 0.01 mol) and ethyl chloroacetate(1.3 ml, 0.01 mol) was refluxed in acetone (50 ml) with anhydrous K2CO3 (2.76 g, 0.02 mol) for 5 h on a water bath. The reaction mixture was cooled to room temperature and filtered to remove the K2CO3 and the filtrate was concentrated over water bath to obtain the title compound. It was then recrystallized using acetonitrile [m.p.:335–338 K]. Analysis for C14H13BrO3: Found(Calculated): C 54.31 (54.39), H 4.19% (4.24%).

Refinement top

All H atoms were found in a difference map, but geometrically positioned and refined with fixed individual displacement parameters [U(H) = 1.2 Ueq(C) or U(H) = 1.5 Ueq(Cmethyl)] using a riding model with C—H ranging from 0.95 Å to 0.99 Å.

Structure description top

The title compound is an intermediate in the preparation of naproxen, a non-steroidal anti-inflammatory drug (NSAID) commonly used for the reduction of high to extreme pain, fever, inflammation and stiffness caused by conditions such as osteoarthritis, rheumatoid arthritis, psoriatic arthritis, gout, ankylosing spondylitis, injury. Naproxen is a member of the 2-arylpropionic acid (profen) family of NSAIDs. The structures the related compounds viz., naproxen (Ravikumar et al., 1985), 6-methoxy-2-naphthyl acetic acid ester-glycolamide (Sharma et al., 2004), 1-(5-chloro-6-methoxynaphthalen-2-yl)propan-1-one (Ye et al., 2006), complex of a lisuride derivative and (S)-naproxen (Bachechi et al., 1997), absolute configuration of (R)-1-phenylethylammonium (S)-2-(6-methoxy-2-naphthyl)propionate (Dupont et al., 1996), N'-isopropylidene-6-methoxy-2-naphthohydrazide (Sarojini et al., 2007), ethyl 6-methoxy-2-naphthoate (Yathirajan et al., 2007) have been published. A new derivative was prepared and its crystal structure is reported.

Geometric parameters of the title compound are in the usual ranges. Neglecting the H atoms, the molecule comprises two planar halves, the bromonaphthyl moiety [r.m.s. deviation 0.010 Å] and the ethoxycarbonylmethoxy moiety [r.m.s. deviation 0.018 Å]. The dihedral angle between these moieties is 79.23 (7)°. The crystal packing is stabilized by a weak C—H···O hydrogen bond.

For related literature, see: Bachechi et al. (1997); Dupont et al. (1996); Ravikumar et al. (1985); Sarojini et al. (2007); Sharma et al. (2004); Yathirajan et al. (2007); Ye et al. (2006).

Computing details top

Data collection: X-AREA (Stoe & Cie, 2001); cell refinement: X-AREA (Stoe & Cie, 2001); data reduction: X-AREA (Stoe & Cie, 2001); program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: XP in SHELXTL-Plus (Sheldrick, 1991); software used to prepare material for publication: SHELXL97 (Sheldrick, 1997).

Figures top
[Figure 1] Fig. 1. Perspective view of the title compound with the atom numbering; displacement ellipsoids are at the 50% probability level.
[Figure 2] Fig. 2. The formation of the title compound.
Ethyl (6-bromo-2-naphthyloxy)acetate top
Crystal data top
C14H13BrO3F(000) = 624
Mr = 309.15Dx = 1.582 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ynCell parameters from 9086 reflections
a = 4.9979 (5) Åθ = 2.7–25.7°
b = 9.3847 (7) ŵ = 3.16 mm1
c = 27.778 (3) ÅT = 173 K
β = 94.857 (8)°Block, colourless
V = 1298.2 (2) Å30.31 × 0.25 × 0.23 mm
Z = 4
Data collection top
Stoe IPDSII two-circle
diffractometer
2376 independent reflections
Radiation source: fine-focus sealed tube2076 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.063
ω scansθmax = 25.4°, θmin = 2.6°
Absorption correction: multi-scan
(MULABS; Spek, 2003; Blessing, 1995)
h = 66
Tmin = 0.441, Tmax = 0.530k = 1110
9302 measured reflectionsl = 3329
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.040H-atom parameters constrained
wR(F2) = 0.103 w = 1/[σ2(Fo2) + (0.0623P)2 + 0.6519P]
where P = (Fo2 + 2Fc2)/3
S = 1.05(Δ/σ)max < 0.001
2376 reflectionsΔρmax = 0.58 e Å3
164 parametersΔρmin = 0.86 e Å3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 1997), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.0201 (18)
Crystal data top
C14H13BrO3V = 1298.2 (2) Å3
Mr = 309.15Z = 4
Monoclinic, P21/nMo Kα radiation
a = 4.9979 (5) ŵ = 3.16 mm1
b = 9.3847 (7) ÅT = 173 K
c = 27.778 (3) Å0.31 × 0.25 × 0.23 mm
β = 94.857 (8)°
Data collection top
Stoe IPDSII two-circle
diffractometer
2376 independent reflections
Absorption correction: multi-scan
(MULABS; Spek, 2003; Blessing, 1995)
2076 reflections with I > 2σ(I)
Tmin = 0.441, Tmax = 0.530Rint = 0.063
9302 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0400 restraints
wR(F2) = 0.103H-atom parameters constrained
S = 1.05Δρmax = 0.58 e Å3
2376 reflectionsΔρmin = 0.86 e Å3
164 parameters
Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
Br10.71291 (7)0.13541 (4)0.159251 (11)0.04132 (18)
O10.3202 (4)0.2554 (2)0.43981 (7)0.0302 (5)
O20.5705 (4)0.5159 (2)0.43859 (8)0.0329 (5)
O30.1838 (4)0.62828 (18)0.44924 (8)0.0245 (4)
C10.1656 (6)0.3806 (3)0.44683 (11)0.0258 (6)
H1A0.09230.37600.47880.031*
H1B0.01250.38490.42180.031*
C20.3349 (5)0.5135 (3)0.44403 (9)0.0212 (6)
C30.3183 (6)0.7654 (3)0.44642 (12)0.0318 (7)
H3A0.38780.77750.41430.038*
H3B0.47080.77190.47150.038*
C40.1136 (8)0.8775 (3)0.45435 (16)0.0451 (9)
H4A0.19580.97200.45250.068*
H4B0.04750.86460.48630.068*
H4C0.03650.86940.42940.068*
C110.3974 (5)0.2311 (3)0.39419 (10)0.0242 (6)
C120.6027 (6)0.1268 (3)0.39287 (12)0.0294 (6)
H120.67350.08220.42190.035*
C130.6977 (6)0.0911 (3)0.35017 (11)0.0311 (6)
H130.83530.02140.34970.037*
C140.5957 (6)0.1557 (3)0.30589 (11)0.0252 (6)
C150.6936 (6)0.1211 (3)0.26118 (12)0.0302 (7)
H150.83440.05360.25980.036*
C160.5853 (6)0.1848 (3)0.21983 (11)0.0307 (6)
C170.3772 (6)0.2856 (3)0.22061 (11)0.0342 (7)
H170.30240.32760.19140.041*
C180.2840 (6)0.3222 (3)0.26353 (12)0.0337 (7)
H180.14560.39150.26410.040*
C190.3897 (5)0.2589 (3)0.30763 (10)0.0248 (6)
C200.2940 (5)0.2957 (3)0.35258 (11)0.0275 (6)
H200.15730.36560.35380.033*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Br10.0533 (3)0.0473 (3)0.0245 (2)0.01467 (14)0.01019 (15)0.00939 (13)
O10.0420 (11)0.0227 (10)0.0276 (11)0.0120 (8)0.0127 (9)0.0034 (8)
O20.0215 (11)0.0365 (11)0.0417 (13)0.0050 (8)0.0074 (9)0.0026 (10)
O30.0249 (9)0.0192 (10)0.0301 (11)0.0044 (7)0.0067 (8)0.0016 (7)
C10.0304 (14)0.0196 (13)0.0291 (16)0.0055 (10)0.0115 (12)0.0004 (11)
C20.0255 (14)0.0241 (13)0.0143 (13)0.0055 (10)0.0030 (10)0.0011 (10)
C30.0334 (15)0.0244 (14)0.0387 (18)0.0039 (11)0.0093 (13)0.0006 (13)
C40.059 (2)0.0210 (15)0.058 (2)0.0044 (14)0.0215 (19)0.0020 (14)
C110.0295 (13)0.0185 (12)0.0253 (15)0.0024 (10)0.0071 (11)0.0008 (11)
C120.0351 (15)0.0256 (14)0.0280 (16)0.0111 (11)0.0059 (12)0.0043 (11)
C130.0352 (15)0.0304 (15)0.0283 (16)0.0129 (12)0.0051 (12)0.0014 (13)
C140.0295 (14)0.0205 (13)0.0256 (15)0.0016 (10)0.0031 (11)0.0039 (11)
C150.0352 (15)0.0261 (15)0.0297 (16)0.0005 (11)0.0057 (13)0.0044 (12)
C160.0373 (15)0.0307 (15)0.0246 (15)0.0110 (12)0.0058 (12)0.0053 (13)
C170.0412 (16)0.0340 (16)0.0265 (16)0.0065 (13)0.0021 (13)0.0047 (13)
C180.0365 (16)0.0328 (16)0.0316 (17)0.0061 (13)0.0012 (12)0.0032 (14)
C190.0272 (13)0.0194 (13)0.0279 (15)0.0003 (10)0.0019 (11)0.0003 (11)
C200.0291 (14)0.0227 (14)0.0312 (16)0.0089 (11)0.0056 (11)0.0021 (12)
Geometric parameters (Å, º) top
Br1—C161.907 (3)C11—C121.421 (4)
O1—C111.374 (3)C12—C131.357 (4)
O1—C11.428 (3)C12—H120.9500
O2—C21.200 (3)C13—C141.426 (4)
O3—C21.330 (3)C13—H130.9500
O3—C31.457 (3)C14—C151.411 (4)
C1—C21.513 (4)C14—C191.417 (4)
C1—H1A0.9900C15—C161.366 (4)
C1—H1B0.9900C15—H150.9500
C3—C41.497 (4)C16—C171.407 (5)
C3—H3A0.9900C17—C181.360 (5)
C3—H3B0.9900C17—H170.9500
C4—H4A0.9800C18—C191.423 (4)
C4—H4B0.9800C18—H180.9500
C4—H4C0.9800C19—C201.417 (4)
C11—C201.367 (4)C20—H200.9500
C11—O1—C1117.4 (2)C13—C12—H12120.0
C2—O3—C3116.1 (2)C11—C12—H12120.0
O1—C1—C2111.1 (2)C12—C13—C14121.5 (3)
O1—C1—H1A109.4C12—C13—H13119.2
C2—C1—H1A109.4C14—C13—H13119.2
O1—C1—H1B109.4C15—C14—C19119.6 (3)
C2—C1—H1B109.4C15—C14—C13122.4 (3)
H1A—C1—H1B108.0C19—C14—C13118.0 (3)
O2—C2—O3124.8 (3)C16—C15—C14119.8 (3)
O2—C2—C1125.5 (2)C16—C15—H15120.1
O3—C2—C1109.7 (2)C14—C15—H15120.1
O3—C3—C4106.8 (2)C15—C16—C17121.5 (3)
O3—C3—H3A110.4C15—C16—Br1119.8 (2)
C4—C3—H3A110.4C17—C16—Br1118.7 (2)
O3—C3—H3B110.4C18—C17—C16119.5 (3)
C4—C3—H3B110.4C18—C17—H17120.3
H3A—C3—H3B108.6C16—C17—H17120.3
C3—C4—H4A109.5C17—C18—C19121.3 (3)
C3—C4—H4B109.5C17—C18—H18119.4
H4A—C4—H4B109.5C19—C18—H18119.4
C3—C4—H4C109.5C20—C19—C14119.8 (3)
H4A—C4—H4C109.5C20—C19—C18121.9 (3)
H4B—C4—H4C109.5C14—C19—C18118.3 (3)
C20—C11—O1126.2 (2)C11—C20—C19120.3 (2)
C20—C11—C12120.4 (3)C11—C20—H20119.8
O1—C11—C12113.4 (3)C19—C20—H20119.8
C13—C12—C11120.0 (3)
C11—O1—C1—C270.4 (3)C14—C15—C16—C170.2 (4)
C3—O3—C2—O22.1 (4)C14—C15—C16—Br1178.8 (2)
C3—O3—C2—C1178.9 (2)C15—C16—C17—C181.0 (5)
O1—C1—C2—O22.8 (4)Br1—C16—C17—C18179.9 (2)
O1—C1—C2—O3178.1 (2)C16—C17—C18—C191.1 (5)
C2—O3—C3—C4178.7 (3)C15—C14—C19—C20178.9 (3)
C1—O1—C11—C2015.6 (4)C13—C14—C19—C200.7 (4)
C1—O1—C11—C12165.1 (2)C15—C14—C19—C181.3 (4)
C20—C11—C12—C130.2 (5)C13—C14—C19—C18179.0 (3)
O1—C11—C12—C13179.5 (3)C17—C18—C19—C20179.8 (3)
C11—C12—C13—C140.2 (5)C17—C18—C19—C140.1 (4)
C12—C13—C14—C15179.3 (3)O1—C11—C20—C19179.0 (3)
C12—C13—C14—C190.3 (4)C12—C11—C20—C190.3 (4)
C19—C14—C15—C161.4 (4)C14—C19—C20—C110.7 (4)
C13—C14—C15—C16179.0 (3)C18—C19—C20—C11179.0 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C1—H1A···O3i0.992.523.499 (3)169
Symmetry code: (i) x, y+1, z+1.

Experimental details

Crystal data
Chemical formulaC14H13BrO3
Mr309.15
Crystal system, space groupMonoclinic, P21/n
Temperature (K)173
a, b, c (Å)4.9979 (5), 9.3847 (7), 27.778 (3)
β (°) 94.857 (8)
V3)1298.2 (2)
Z4
Radiation typeMo Kα
µ (mm1)3.16
Crystal size (mm)0.31 × 0.25 × 0.23
Data collection
DiffractometerStoe IPDSII two-circle
Absorption correctionMulti-scan
(MULABS; Spek, 2003; Blessing, 1995)
Tmin, Tmax0.441, 0.530
No. of measured, independent and
observed [I > 2σ(I)] reflections
9302, 2376, 2076
Rint0.063
(sin θ/λ)max1)0.604
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.040, 0.103, 1.05
No. of reflections2376
No. of parameters164
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.58, 0.86

Computer programs: X-AREA (Stoe & Cie, 2001), SHELXS97 (Sheldrick, 1990), SHELXL97 (Sheldrick, 1997), XP in SHELXTL-Plus (Sheldrick, 1991).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C1—H1A···O3i0.992.523.499 (3)168.5
Symmetry code: (i) x, y+1, z+1.
 

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